Living With Statins - Interventional Exercise Study

NCT02796378 | Unknown Phase 4

• 1 other identifier: LIFESTAT - Exercise study
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Background. Statins are cholesterol lowering drugs that are prescribed to lower the risk of cardio-vascular diseases. The use of statins has increased markedly and it is now one of the most prescribed drugs in the world. More than 600,000 people in Denmark are taking statins on a daily basis, approximately 40 % of these are taking the medication without having any other risk factors for cardio-vascular diseases than elevated blood-cholesterol i.e. they are in primary prevention. Statins are not without side effects and studies have shown that there is an elevated risk of developing diabetes when taking statins. This has led to an increased debate about the use of statins in primary prevention. Furthermore a large meta-analysis has shown that to prevent one event of cardio-vascular disease, it is necessary to treat 200 people for 3-5 years. These data suggest that more conservative use of statins to prevent CVD in otherwise healthy individuals at low risk for future CVD may be warranted. Other side effects of statins are muscle myalgia, muscle cramps and fatigue which potentially can prevent a physically active lifestyle. The biomedical background of these side effects is not fully elucidated but it has been shown that there is a link to decreasing levels of an important enzyme, Q10, which plays a role in muscle energy metabolism. Hypothesis The overarching research question is: why does statin treatment cause muscle pain? Does statin treatment impair (or even prohibit) physical exercise training? Furthermore the following questions will be investigated: A. Does statin treatment cause:

1. 1.Decreased muscle strength?
2. 2.Skeletal muscle inflammation?
3. 3.Decreased mitochondrial respiratory function? B. Abnormal glucose homeostasis?

Conditions

Cardiovascular Disease; Diabetes Mellitus

Keywords

physical activity; statin therapy; diabetes mellitus; cardiovascular disease; Q10-supplementation

Outcome Measures

Primary Outcomes (1)

• Physical performance measured by VO2-max

  Difference in physical performance measured by VO2-max (mlO2/min/kgBW) in the three different intervention groups.

  8 weeks

Secondary Outcomes (4)

• Myalgia measured by VAS

  8 weeks

• Difference in muscle strength measured by KinCom dynamometer and PowerRig

  8 weeks

• Difference in glucose metabolism measured by hyperinsulinemic euglycemic clamp

  8 weeks

• Difference in mitochondrial function measured by respirometry

  8 weeks

Study Arms (3)

Training+Simvastatin+Q10-placebo

ACTIVE COMPARATOR

Training+Simvastatin+Q10-placebo. 8 Weeks of exercise training on a bicycle ergometer three times a week and 40 mg of Simvastatin pr day and Q10-placebo.

Drug: Training+Simvastatin+Q10-placebo

Training+Simvastatin-placebo+Q10-placebo

PLACEBO COMPARATOR

Training+Simvastatin-placebo+Q10-placebo. 8 Weeks of exercise training on a bicycle ergometer three times a week, Simvastatin-placebo and Q10-placebo.

Drug: Training+Simvastatin-placebo+Q10-placebo

Training+Simvastatin+Q10

ACTIVE COMPARATOR

Training+Simvastatin+Q10. 8 Weeks of exercise training on a bicycle ergometer three times a week and 40 mg of Simvastatin pr day in combination with 400 mg of oral supplementation with Q10.

Drug: Training+Simvastatin+Q10

Interventions

Training+Simvastatin+Q10-placebo DRUG

8 weeks of exercise training on a bycycle ergometer 3 times/week combined with Simvastatin 40 mg/day and Q10-placebo.

Also known as: SP

Training+Simvastatin+Q10-placebo

Training+Simvastatin-placebo+Q10-placebo DRUG

8 weeks of exercise training on a bycycle ergometer 3 times/week combined with Simvastatin-placebo and Q10-placebo.

Also known as: PL

Training+Simvastatin-placebo+Q10-placebo

Training+Simvastatin+Q10 DRUG

8 weeks of exercise training on a bycycle ergometer 3 times/week combined with Simvastatin 40 mg/day and Q10 400 mg/day.

Also known as: Simvastatin KRKA, SQ

Training+Simvastatin+Q10

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Elevated blood-cholesterol

You may not qualify if:

• Cholesterol-lowering drugs
• Diabetes Mellitus
• Cardiovascular disease such as arrythmia, ischaemic heart disease.
• Musculoskeletal disorders preventing the subject to perform physical training
• Mental disorders preventing the subject to understand the project description.

Sponsors & Collaborators

• University of Copenhagen: lead

Study Sites (1)

University of Copenhagen

Copenhagen, 2200, Denmark

Location

Related Publications (13)

• Boushel R, Gnaiger E, Schjerling P, Skovbro M, Kraunsoe R, Dela F. Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia. 2007 Apr;50(4):790-6. doi: 10.1007/s00125-007-0594-3. Epub 2007 Feb 15.

  PMID: 17334651 BACKGROUND

• Ebrahim S, Casas JP. Statins for all by the age of 50 years? Lancet. 2012 Aug 11;380(9841):545-7. doi: 10.1016/S0140-6736(12)60694-1. Epub 2012 May 17. No abstract available.

  PMID: 22607823 BACKGROUND

• Larsen S, Hey-Mogensen M, Rabol R, Stride N, Helge JW, Dela F. The influence of age and aerobic fitness: effects on mitochondrial respiration in skeletal muscle. Acta Physiol (Oxf). 2012 Jul;205(3):423-32. doi: 10.1111/j.1748-1716.2012.02408.x. Epub 2012 Feb 11.

  PMID: 22212519 BACKGROUND

• Larsen S, Nielsen J, Hansen CN, Nielsen LB, Wibrand F, Stride N, Schroder HD, Boushel R, Helge JW, Dela F, Hey-Mogensen M. Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. J Physiol. 2012 Jul 15;590(14):3349-60. doi: 10.1113/jphysiol.2012.230185. Epub 2012 May 14.

  PMID: 22586215 BACKGROUND

• Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Andersen JL, Madsbad S, Worm D, Helge JW, Dela F. Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes. Diabetologia. 2011 Jun;54(6):1427-36. doi: 10.1007/s00125-011-2098-4. Epub 2011 Mar 18.

  PMID: 21424396 BACKGROUND

• Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Bang LE, Bundgaard H, Nielsen LB, Helge JW, Dela F. Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance. J Am Coll Cardiol. 2013 Jan 8;61(1):44-53. doi: 10.1016/j.jacc.2012.09.036.

  PMID: 23287371 BACKGROUND

• Singh P, Kohr D, Kaps M, Blaes F. Skeletal muscle cell MHC I expression: implications for statin-induced myopathy. Muscle Nerve. 2010 Feb;41(2):179-84. doi: 10.1002/mus.21479.

  PMID: 19813190 BACKGROUND

• Cholesterol Treatment Trialists' (CTT) Collaborators; Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012 Aug 11;380(9841):581-90. doi: 10.1016/S0140-6736(12)60367-5. Epub 2012 May 17.

  PMID: 22607822 BACKGROUND

• Parker BA, Thompson PD. Effect of statins on skeletal muscle: exercise, myopathy, and muscle outcomes. Exerc Sport Sci Rev. 2012 Oct;40(4):188-94. doi: 10.1097/JES.0b013e31826c169e.

  PMID: 23000957 BACKGROUND

• Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren WM, Albus C, Benlian P, Boysen G, Cifkova R, Deaton C, Ebrahim S, Fisher M, Germano G, Hobbs R, Hoes A, Karadeniz S, Mezzani A, Prescott E, Ryden L, Scherer M, Syvanne M, Scholte Op Reimer WJ, Vrints C, Wood D, Zamorano JL, Zannad F; Comitato per Linee Guida Pratiche (CPG) dell'ESC. [European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts)]. G Ital Cardiol (Rome). 2013 May;14(5):328-92. doi: 10.1714/1264.13964. No abstract available. Italian.

  PMID: 23612326 BACKGROUND

• Ray KK, Seshasai SR, Erqou S, Sever P, Jukema JW, Ford I, Sattar N. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med. 2010 Jun 28;170(12):1024-31. doi: 10.1001/archinternmed.2010.182.

  PMID: 20585067 BACKGROUND

• Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012 Aug 11;380(9841):565-71. doi: 10.1016/S0140-6736(12)61190-8.

  PMID: 22883507 BACKGROUND

• Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD004816. doi: 10.1002/14651858.CD004816.pub4.

  PMID: 21249663 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases; Diabetes Mellitus; Motor Activity

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Behavior

Study Officials

• Flemming Dela, MD, MDSci

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 27, 2016
• First Posted: June 10, 2016
• Study Start: June 1, 2016
• Primary Completion: July 1, 2021
• Study Completion: December 1, 2021
• Last Updated: February 11, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)